Saturday, September 20, 2014

Epigenetics

““Epigenetics” refers to covalent modification of DNA, protein, or RNA, resulting in changes to the function and/or regulation of these molecules, without altering their primary sequences.”  The Greek prefix “epi” means “on top of” or “above”, so epigenetics literally means regulation above the level of genetic mechanisms. In some cases, epigenetic modifications are passed on to future generations, but in other instances they are dynamic and change in response to environmental stimuli. Nearly every aspect of biology is influenced by epigenetics, making it one of the most important fields in science.
The importance of nature versus nurture has long been disputed. It cannot be denied that environment greatly influences how a child grows and develops, nor can it be denied that our DNA is the blueprint that makes us who we are. Epigenetics merges these two seemingly contradictory lines of thought to explain how environmental factors cause physical modifications to DNA and its associated structures, which result in altered functions.
The big difference between genetic and epigenetic regulation is that epigenetic mechanisms do not involve a change to the DNA sequence, whereas genetic mechanisms involve the primary DNA sequence and changes or mutations to this sequence.  Epigenetic regulation involves the modification of DNA and the proteins associated with DNA, which results in changes to the conformation of DNA and accessibility of other factors to DNA, without a change to the sequence of the DNA. As more factors influencing heredity are discovered, today’s scientists are using epigenetics to decipher the roles of DNA, RNA, proteins, and environment in inheritance. The future of epigenetics will reveal the complexities of cellular differentiation, embryology, the regulation of gene expression, aging, cancer, and other diseases.
The most widely known epigenetic modification is DNA methylation, which is a chemical process that adds a methyl group to DNA. It is highly specific and always happens in a region in which a cytosine nucleotide is located next to a guanine nucleotide that is linked by a phosphate; this is called a CpG site (Egger et al., 2004; Jones & Baylin, 2002; Robertson, 2002). CpG sites are methylated by one of three enzymes called DNA methyltransferases (DNMTs) (Egger et al., 2004; Robertson, 2002). Inserting methyl groups changes the appearance and structure of DNA, modifying a gene's interactions with the machinery within a cell's nucleus that is needed for transcription. DNA methylation is used in some genes to differentiate which gene copy is inherited from the father and which gene copy is inherited from the mother, a phenomenon known as imprinting.
The first human disease to be linked to epigenetics was cancer in 1983. Researchers found that diseased tissue from patients with colorectal cancer had less DNA methylation than normal tissue from the same patients (Feinberg & Vogelstein, 1983). Because methylated genes are typically turned off, loss of DNA methylation can cause abnormally high gene activation by altering the arrangement of chromatin. On the other hand, too much methylation can undo the work of protective tumor suppressor genes. CpG islands become excessively methylated in cancer cells, thereby causing genes that should not be silenced to turn off. This abnormality is the trademark epigenetic change that occurs in tumors and happens early in the development of cancer (Egger et al., 2004; Robertson, 2002; Jones & Baylin, 2002).

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